Vaginal speculum lubrication and its effects on cervical cytology and microbiology.
The prevailing approach to Papanicolaou (Pap) and endocervical Gen-Probe(R) screening is to use an unlubricated vaginal speculum because of concerns that gel lubricant interferes with Pap smear adequacy and cervical microbiology. This study tests the hypothesis that lubrication of metal specula with a bacteriostatic gel does not increase unsatisfactory cervical cytology or decrease detection rates of endocervical Chlamydia trachomatis or Neisseria gonorrhoeae. At a publicly funded family planning clinic site, each of eight consecutive months was randomly designated by computer as an exclusively gel-lubricated or water-moistened specula use month. The assigned vaginal speculum intervention was used on all patients receiving a Pap smear and/or combination DNA probe assay for endocervical C. trachomatis and N. gonorrhoeae. From July 2003 through February 2004, 3460 Pap smears and 5535 combination probe assays for C. trachomatis and N. gonorrhoeae were collected from 6538 patients. During the 4 months of gel lubricant use, the rate of unsatisfactory cytology was 1.1% compared to 1.5% during the 4 months of water lubrication [odds ratio (OR) 0.74; 95% confidence interval (CI) 0.41-1.35]. During the 4 months of gel lubricant use, the detection rate for endocervical C. trachomatis was 1.5% compared to 1.5% (OR 1.05; 95% CI 0.67-1.62) in water lubricant months. The study population N. gonorrhoeae infection rate was too low to statistically analyze. The use of a small amount of gel lubricant on metal vaginal specula did not increase unsatisfactory cytology or decrease endocervical C. trachomatis detection rates when compared to water lubricant.


MR-guided percutaneous angioplasty: assessment of tracking safety, catheter handling and functionality.
Magnetic resonance (MR)-guided percutaneous vascular interventions have evolved to a practical possibility with the advent of open-configuration MR systems and real-time tracking techniques. The purpose of this study was to assess an MR-tracking percutaneous transluminal angioplasty (PTA) catheter with regard to its safety profile and functionality. Real-time, biplanar tracking of the PTA catheter was made possible by incorporating a small radiofrequency (RF) coil in the catheter tip and connecting it to a coaxial cable embedded in the catheter wall. To evaluate potentially hazardous thermal effects due to the incorporation of the coil, temperature measurements were performed within and around the coil under various scanning and tracking conditions at 1.5 Tesla (T). Catheter force transmission and balloon-burst pressure of the MR-tracking PTA catheter were compared with those of a standard PTA catheter. The dilatative capability of the angioplasty balloon was assessed in vitro as well as in vivo, in an isolated femoral artery segment in a swine. The degree of heating at the RF coil was directly proportional to the power of the RF pulses. Heating was negligible with MR tracking, conventional spin-echo and low-flip gradient-echo sequences. Sequences with higher duty cycles, such as fast spin echo, produced harmful heating effects. Force transmission of the MR-tracking PTA catheter was slightly inferior to that of the standard PTA catheter, while balloon-burst pressures were similar to those of conventional catheters. The MR-tracking PTA catheter functioned well both in vitro and in vivo. The in vivo use of an MR-tracking PTA catheter is safe under most scanning conditions.


Give It a Tug and Feel It Grow: Extending Body Perception Through the Universal Nature of Illusory Finger Stretching.
If British teenage boy asks you to pull his finger, it is usually an indication that he simultaneously wishes to break wind. If you were to tell him that you could pull his finger and stretch it to twice its length, you might expect a similarly irreverent response yet when we pulled the fingers of nearly 600 children and adolescents, 93% reported the illusion of stretching. Grossly distorted body representations need not be the preserve of clinical disorders and can reliably be induced in healthy participants across all ages.


Sources of sport confidence, imagery type and performance among competitive athletes: the mediating role of sports confidence.
This study explored the mediating role of sport confidence upon (1) sources of sport confidence-performance relationship and (2) imagery-performance relationship. Participants were 157 competitive athletes who completed state measures of confidence level/sources, imagery type and performance within one hour after competition. Among the current sample, confirmatory factor analysis revealed appropriate support for the nine-factor SSCQ and the five-factor SIQ. Mediational analysis revealed that sport confidence had a mediating influence upon the achievement source of confidence-performance relationship. In addition, both cognitive and motivational imagery types were found to be important sources of confidence, as sport confidence mediated imagery type- performance relationship. Findings indicated that athletes who construed confidence from their own achievements and report multiple images on a more frequent basis are likely to benefit from enhanced levels of state sport confidence and subsequent performance.


Role of thioredoxins in the response of Saccharomyces cerevisiae to oxidative stress induced by hydroperoxides.
Glutaredoxins and thioredoxins are highly conserved, small, heat-stable oxidoreductases. The yeast Saccharomyces cerevisiae contains two gene pairs encoding cytoplasmic glutaredoxins (GRX1, GRX2) and thioredoxins (TRX1, TRX2), and we have used multiple mutants to determine their roles in mediating resistance to oxidative stress caused by hydroperoxides. Our data indicate that TRX2 plays the predominant role, as mutants lacking TRX2 are hypersensitive, and mutants containing TRX2 are resistant to these oxidants. However, the requirement for TRX2 is only apparent during stationary phase growth, and we present three lines of evidence that the thioredoxin isoenzymes actually have redundant activities as antioxidants. First, the trx1 and trx2 mutants show wild-type resistance to hydroperoxide during exponential phase growth; secondly, overexpression of either TRX1 or TRX2 leads to increased resistance to hydroperoxides; and, thirdly, both Trx1 and Trx2 are equally able to act as cofactors for the thioredoxin peroxidase, Tsa1. The antioxidant activity of thioredoxins is required for both the survival of yeast cells as well as protection against oxidative stress during stationary phase growth, and correlates with an increase in the expression of both TRX1 and TRX2. We show that the requirement for thioredoxins during this growth phase is dependent on their activity as cofactors for the antioxidant enzyme Tsa1, and for regulation of the redox state and protein-bound levels of the low-molecular-weight antioxidant glutathione.


Adolescent suicidal ideation: a comparison of incarcerated and school-based samples.
The aim of this study was to investigate suicidal ideations and associated psychopathology in two groups of adolescents, a sample of detained youth and a general population sample. In both groups the comparisons of mental health characteristics between suicidal ideators and non-suicidal youth were conducted separately for girls and boys. The study sample consisted of 290 delinquent adolescents [228 boys and 62 girls] from three Flemish juvenile detention centers and 1,548 adolescents [811 boys and 737 girls] from an age-matched school-based sample. Both groups were administered the Social and Health Assessment [SAHA], a self-report survey investigating levels of psychopathology [internalizing and externalizing] and risk-taking behavior. Suicidal ideations during the past year were reported by 21.5% of detained males, compared to 6.7% in the general population. In females, 58.1% of detained individuals reported suicidal thoughts during the past year, compared to 14.4% of the general population. In girls and boys from the general population, both internalizing and externalizing problems were higher in suicidal ideators than in non-suicidal youth, while in the detention group mainly internalizing problems were higher in suicidal ideators. When comparing detention suicidal ideators with those from the general population, male suicidal ideators scored higher on delinquency, while detained female suicidal ideators also scored higher on posttraumatic stress, but lower on prosocial beliefs. Information used in this study was solely based on self-report measures only and limited to Flemish adolescents. Since suicidal ideation is a frequent problem in detained youth, adequate recognition and treatment seems clinically relevant. While both internalizing and externalizing psychopathology may be an indicator of suicidal ideation in the general population, internalizing problems may be the main clinical predictor in detained youth.


Maltose and maltotriose can be formed endogenously in Escherichia coli from glucose and glucose-1-phosphate independently of enzymes of the maltose system.
The maltose system in Escherichia coli consists of cell envelope-associated proteins and enzymes that catalyze the uptake and utilization of maltose and alpha,1-4-linked maltodextrins. The presence of these sugars in the growth medium induces the maltose system (exogenous induction), even though only maltotriose has been identified in vitro as an inducer (O. Raibaud and E. Richet, J. Bacteriol., 169:3059-3061, 1987). Induction is dependent on MalT, the positive regulator protein of the system. In the presence of exogenous glucose, the maltose system is normally repressed because of catabolite repression and inducer exclusion brought about by the phosphotransferase-mediated vectorial phosphorylation of glucose. In contrast, the increase of free, unphosphorylated glucose in the cell induces the maltose system. A ptsG ptsM glk mutant which cannot grow on glucose can accumulate [14C]glucose via galactose permeases. In this strain, internal glucose is polymerized to maltose, maltotriose, and maltodextrins in which only the reducing glucose residue is labeled. This polymerization does not require maltose enzymes, since it still occurs in malT mutants. Formation of maltodextrins from external glucose as well as induction of the maltose system is absent in a mutant lacking phosphoglucomutase, and induction by external glucose could be regained by the addition of glucose-1-phosphate entering the cells via a constitutive glucose phosphate transport system. malQ mutants, which lack amylomaltase, are constitutive for the expression of the maltose genes. This constitutive nature is due to the formation of maltose and maltodextrins from the degradation of glycogen.


Temporal coding in a silicon network of integrate-and-fire neurons.
Spatio-temporal processing of spike trains by neuronal networks depends on a variety of mechanisms distributed across synapses, dendrites, and somata. In natural systems, the spike trains and the processing mechanisms cohere though their common physical instantiation. This coherence is lost when the natural system is encoded for simulation on a general purpose computer. By contrast, analog VLSI circuits are, like neurons, inherently related by their real-time physics, and so, could provide a useful substrate for exploring neuronlike event-based processing. Here, we describe a hybrid analog-digital VLSI chip comprising a set of integrate-and-fire neurons and short-term dynamical synapses that can be configured into simple network architectures with some properties of neocortical neuronal circuits. We show that, despite considerable fabrication variance in the properties of individual neurons, the chip offers a viable substrate for exploring real-time spike-based processing in networks of neurons.


Three-dimensional biomechanics of simulated laryngeal abduction in horses.
To investigate the influence of simulated contraction of the cricoarytenoideus dorsalis (CAD) muscle on the 3-D motion of the arytenoid cartilage. 5 larynges from equine cadavers. Serial computed tomographic scans of each larynx were conducted at 7 incremental forces simulating contraction of medial, lateral, and combined bellies of the left CAD muscle. Three-dimensional reconstruction of radiopaque markers placed at anatomic landmarks on the left arytenoid and cricoid cartilages enabled quantification of marker displacement according to a Cartesian coordinate system. Rotation (roll, pitch, and yaw) of dorsal and ventral arytenoid planes was calculated relative to a plane formed by the coordinates of 3 markers on the cricoid cartilage by use of Euler angles. Displacement and rotational data showed that rocking motion occurs throughout arytenoid abduction and most of the rotational component is attributable to pitch; greater pitch was associated with action of the lateral belly. Roll of the ventral arytenoid plane was principally associated with action of the medial belly, which counteracted the tendency of the arytenoid cartilage to rotate medially into the rima glottidis lumen. The distance between markers on the arytenoid cartilage was not constant during contraction because of slight deformation of the corniculate process of the arytenoid cartilage, therefore indicating that the arytenoid cartilage is not a rigid body during abduction. Arytenoid cartilage abduction was dependent on the rocking motion elicited by the lateral belly of the CAD muscle; therefore, laryngoplasty suture placement should mimic the action of the lateral, rather than the medial, muscle belly.


Predictors of early growth in academic achievement: the head-toes-knees-shoulders task.
Children's behavioral self-regulation and executive function (EF; including attentional or cognitive flexibility, working memory, and inhibitory control) are strong predictors of academic achievement. The present study examined the psychometric properties of a measure of behavioral self-regulation called the Head-Toes-Knees-Shoulders (HTKS) by assessing construct validity, including relations to EF measures, and predictive validity to academic achievement growth between prekindergarten and kindergarten. In the fall and spring of prekindergarten and kindergarten, 208 children (51% enrolled in Head Start) were assessed on the HTKS, measures of cognitive flexibility, working memory (WM), and inhibitory control, and measures of emergent literacy, mathematics, and vocabulary. For construct validity, the HTKS was significantly related to cognitive flexibility, working memory, and inhibitory control in prekindergarten and kindergarten. For predictive validity in prekindergarten, a random effects model indicated that the HTKS significantly predicted growth in mathematics, whereas a cognitive flexibility task significantly predicted growth in mathematics and vocabulary. In kindergarten, the HTKS was the only measure to significantly predict growth in all academic outcomes. An alternative conservative analytical approach, a fixed effects analysis (FEA) model, also indicated that growth in both the HTKS and measures of EF significantly predicted growth in mathematics over four time points between prekindergarten and kindergarten. Results demonstrate that the HTKS involves cognitive flexibility, working memory, and inhibitory control, and is substantively implicated in early achievement, with the strongest relations found for growth in achievement during kindergarten and associations with emergent mathematics.


A rational tool for the umami evaluation of peptides based on multi-techniques.
Umami peptides have become of key interest in the development of flavoring agents. However, the lack of known umami peptides further prevents the understanding of the umami mechanism. The famous pufferfish (Takifugu flavidus) is a great resource for novel umami peptides, and we further analyze the umami characteristics of peptides based on multi-evaluation. In this study, five novel umami peptides, DF9, TK18, AK11, IK10, and GT12 were found; DF9 having the highest umami intensity, followed by AK11. Moreover, biosensor results showed DF9 with the lowest Ka value of 6.85 × 10-13 mol/L, followed by AK11. These data are mostly in agreement with sensory evaluation and fully reveal the umami mechanism of peptides. Quantum chemical and molecular docking demonstrated active site D in peptides bound with T1R1 receptor. Our results open up new strategies to estimate the taste characteristics of umami peptides and provide rational tools for screening umami peptides in food.


Goal-Directed Correlates and Neurobiological Underpinnings of Adolescent Identity: A Multimethod Multisample Longitudinal Approach.
This multimethod multisample longitudinal study examined how neurological substrates associated with goal directedness and information seeking are related to adolescents' identity. Self-reported data on goal-directedness were collected across three biannual waves in Study 1. Identity was measured one wave later. Study 1 design and measurements were repeated in Study 2 and extended with structural brain data (nucleus accumbens [NAcc] and prefrontal cortex gray matter volume [PFC]), collected across three biannual waves. Study 1 included 497 adolescents (Mage T1 = 13.03 years) and Study 2 included 131 adolescents (Mage T1 = 14.69 years). Using latent growth curve models, goal directedness, NAcc, and PFC volume predicted a stronger identity one wave later. These findings provide crucial new insights in the underlying neurobiological architecture of identity.


Critical Review of Advances in Engineering Nanomaterial Adsorbents for Metal Removal and Recovery from Water: Mechanism Identification and Engineering Design.
Nanomaterial adsorbents (NAs) have shown promise to efficiently remove toxic metals from water, yet their practical use remains challenging. Limited understanding of adsorption mechanisms and scaling up evaluation are the two main obstacles. To fully realize the practical use of NAs for metal removal, we review the advanced tools and chemical principles to identify mechanisms, highlight the importance of adsorption capacity and kinetics on engineering design, and propose a systematic engineering scenario for full-scale NA implementation. Specifically, we provide in-depth insight for using density functional theory (DFT) and/or X-ray absorption fine structure (XAFS) to elucidate adsorption mechanisms in terms of active site verification and molecular interaction configuration. Furthermore, we discuss engineering issues for designing, scaling, and operating NA systems, including adsorption modeling, reactor selection, and NA regeneration, recovery, and disposal. This review also prioritizes research needs for (i) determining NA microstructure properties using DFT, XAFS, and machine learning and (ii) recovering NAs from treated water. Our critical review is expected to guide and advance the development of highly efficient NAs for engineering applications.


Preoperative demonstration of the neurovascular compression characteristics with special emphasis on the degree of compression, using high-resolution magnetic resonance imaging: a prospective study, with comparison to surgical findings, in 100 consecutive patients who underwent microvascular decompression for trigeminal neuralgia.
Surgical outcome after microvascular decompression (MVD) for primary trigeminal neuralgia (TN) has been demonstrated as being related to the characteristics of the neurovascular compression (NVC), especially to the degree of compression exerted on the root. Therefore, preoperative determination of the NVC features could be of great value to the neurosurgeon, for evaluation of conflicting nature, exact localization, direction and degree of compression. This study deals with the predictive value of MRI in detecting and assessing features of vascular compression in 100 consecutive patients who underwent MVD for TN. The study included 100 consecutive patients with primary TN who were submitted to a preoperative 3D MRI 1.5 T with T2 high-resolution, TOF-MRA, and T1-Gadolinium. Image analysis was performed by an independent observer blinded to the operative findings and compared with surgical data. In 88 cases, image analysis showed NVC features that coincided with surgical findings. There were no false-positive results. Among 12 patients that did not show NVC at image analysis, nine did not have NVC at intraoperative observation, resulting in three false-negative cases. MRI sensitivity was 96.7% (88/91) and specificity 100% (9/9). Image analysis correctly identified compressible vessel in 80 of the 91 cases and degree of compression in 77 of the 91 cases. Kappa-coefficient predicting degree of root compression was 0.746, 0.767, and 0.86, respectively, for Grades I (simple contact), II (distortion), and III (marked indentation; p < 0.01). 3D T2 high-resolution in combination with 3D TOF-MRA and 3D T1-Gadolinium proved to be reliable in detecting NVC and in predicting the degree of the root compression.


IGF-I/PI3K/Akt and IGF-I/MAPK/ERK pathways in vivo in skeletal muscle are regulated by nutrition and contribute to somatic growth in the fine flounder.
The insulin-like growth factor-I (IGF-I) is a key regulator of skeletal muscle growth in vertebrates, promoting mitogenic and anabolic effects through the activation of the MAPK/ERK and the PI3K/Akt signaling pathways. Nutrition also affects skeletal muscle growth, activating intracellular pathways and inducing protein synthesis and accretion. Thus, both hormonal and nutritional signaling regulate muscle mass. In this context, plasma IGF-I levels and the activation of both pathways in response to food were evaluated in the fine flounder using fasting and refeeding trials. The present study describes for the first time in a nonmammalian species that the MAPK/ERK and PI3K/Akt are activated by exogenous circulating IGF-I, as well as showing that the MAPK/ERK pathway activation is modulated by the nutritional status. Also, these results show that there is a time-dependent regulation of IGF-I plasma levels and its signaling pathways in muscle. Together, these results suggest that the nutritionally managed IGF-I could be regulating the activation of the MAPK/ERK and the PI3K/Akt signaling pathways differentially according to the nutritional status, triggering different effects in growth parameters and therefore contributing to somatic growth in fish. This study contributes to the understanding of the nutrient regulation of IGF-I and its signaling pathways in skeletal muscle growth in nonmammalian species, therefore providing insight concerning the events controlling somatic growth in vertebrates.


DNA Hypomethylation of miR-30a Mediated the Protection of Hypoxia Postconditioning Against Aged Cardiomyocytes Hypoxia/Reoxygenation Injury Through Inhibiting Autophagy.
Ischemic postconditioning (IPostC) is an endogenous protective mechanism to reduce ischemia-reperfusion (I/R) injury. However, whether IPostC protects aged cardiomyocytes against I/R injury is not fully understood. Considering the protective function of microRNA 30a (miR-30a) against ischemia-induced injury in H9C2 cells, its role in the protective effects of IPostC on I/R injury of aged cardiomyocytes was investigated further.Methods and Results:To mimic I/R and IPostC in vitro, the aged cardiomyocyte model for hypoxia postconditioning (HPostC) treatment was established by 9 days of incubation with 8 mg/mL D-galactose and then followed by exposure to hypoxic environment. HPostC significantly alleviated hypoxia/reoxygenation (H/R) injury and reduced autophagy of aged cardiomyocytes, as evidenced by decreased LC3B-II expression and increased p62 by Western blot. Quantified by quantitative real-time polymerase chain reaction (qRT-PCR), miR-30a was increased in aged cardiomyocytes treated with HPostC compared with I/R injury group. Overexpression of miR-30a by LV3-rno-miR-30a mimic promoted cardioprotective effect of HPostC in aged cardiomyocytes by suppressing BECN1-mediated autophagy, all of which was abrogated by knockdown of miR-30a expression. Epigenetic analyses demonstrated that HPostC reduced DNA methyltransferase 3b-mediated DNA hypomethylation levels at miR-30a promoter, leading to upregulation of miR-30a. HPostC protected aged cardiomyocytes survival against H/R injury via DNMT3b-dependent activation of miR-30a. miR-30a could be a potential therapeutic target for ischemic myocardial infarction.


Comparative analysis of chromosome counts infers three paleopolyploidies in the mollusca.
The study of paleopolyploidies requires the comparison of multiple whole genome sequences. If the branches of a phylogeny on which a whole-genome duplication (WGD) occurred could be identified before genome sequencing, taxa could be selected that provided a better assessment of that genome duplication. Here, we describe a likelihood model in which the number of chromosomes in a genome evolves according to a Markov process with one rate of chromosome duplication and loss that is proportional to the number of chromosomes in the genome and another stochastic rate at which every chromosome in the genome could duplicate in a single event. We compare the maximum likelihoods of a model in which the genome duplication rate varies to one in which it is fixed at zero using the Akaike information criterion, to determine if a model with WGDs is a good fit for the data. Once it has been determined that the data does fit the WGD model, we infer the phylogenetic position of paleopolyploidies by calculating the posterior probability that a WGD occurred on each branch of the taxon tree. Here, we apply this model to a molluscan tree represented by 124 taxa and infer three putative WGD events. In the Gastropoda, we identify a single branch within the Hypsogastropoda and one of two branches at the base of the Stylommatophora. We also identify one or two branches near the base of the Cephalopoda.


Multiple behaviour change intervention and outcomes in recently diagnosed type 2 diabetes: the ADDITION-Plus randomised controlled trial.
The aim of this study was to assess whether or not a theory-based behaviour change intervention delivered by trained and quality-assured lifestyle facilitators can achieve and maintain improvements in physical activity, dietary change, medication adherence and smoking cessation in people with recently diagnosed type 2 diabetes. An explanatory randomised controlled trial was conducted in 34 general practices in Eastern England (Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care-Plus [ADDITION-Plus]). In all, 478 patients meeting eligibility criteria (age 40 to 69 years with recently diagnosed screen or clinically detected diabetes) were individually randomised to receive either intensive treatment (n = 239) or intensive treatment plus a theory-based behaviour change intervention led by a facilitator external to the general practice team (n = 239). Randomisation was central and independent using a partial minimisation procedure to balance stratifiers between treatment arms. Facilitators taught patients skills to facilitate change in and maintenance of key health behaviours, including goal setting, self-monitoring and building habits. Primary outcomes included physical activity energy expenditure (individually calibrated heart rate monitoring and movement sensing), change in objectively measured fruit and vegetable intake (plasma vitamin C), medication adherence (plasma drug levels) and smoking status (plasma cotinine levels) at 1 year. Measurements, data entry and laboratory analysis were conducted with staff unaware of participants' study group allocation. Of 475 participants still alive, 444 (93%; intervention group 95%, comparison group 92%) attended 1-year follow-up. There were no significant differences between groups in physical activity (difference: +1.50 kJ kg(-1) day(-1); 95% CI -1.74, 4.74), plasma vitamin C (difference: -3.84 μmol/l; 95% CI -8.07, 0.38), smoking (OR 1.37; 95% CI 0.77, 2.43) and plasma drug levels (difference in metformin levels: -119.5 μmol/l; 95% CI -335.0, 95.9). Cardiovascular risk factors and self-reported behaviour improved in both groups with no significant differences between groups. For patients with recently diagnosed type 2 diabetes receiving intensive treatment in UK primary care, a facilitator-led individually tailored behaviour change intervention did not improve objectively measured health behaviours or cardiovascular risk factors over 1 year. ISRCTN99175498 FUNDING: The trial is supported by the Medical Research Council, the Wellcome Trust, National Health Service R&D support funding (including the Primary Care Research and Diabetes Research Networks) and National Institute of Health Research under its Programme Grants for Applied Research scheme. The Primary Care Unit is supported by NIHR Research funds. Bio-Rad provided equipment for HbA1c testing during the screening phase.


Research and Scholarship During the COVID-19 Pandemic: A Wicked Problem.
This study focuses on the impacts of the COVID-19 pandemic on research and scholarship at a research university in the United States. Building on studies in higher education policy, we conceptualized the COVID-19 pandemic as a 'wicked problem' that is complex, nonlinear, unique, and requiring urgent solutions. Wicked problems highlight pre-existing struggles, and therefore, recent challenges in higher education inform the methods and the findings of this study. Qualitative and quantitative survey data from 408 faculty, staff, and students explicate the reasons for reduced research output and adaptations made for increased or sustained productivity, health, and wellness that influenced research activities. The analysis showed that most respondents experienced reduced productivity mostly due to increased work responsibilities, limited access to research fields, and inadequate resources. Despite self-reported reduced productivity, participants from the University we studied experienced increases in funding during the pandemic. Thus, the findings also reported on the adaptations for sustained or increased productivity. These included new research pursuits, participation in conference and learning opportunities across geographic regions, and purchase of computer equipment/accessories for home offices. A small percentage of respondents mentioned improved health and well-being; however, many linked reduced research activities to health and well-being issues such as anxiety and fear about the pandemic and being overwhelmed due to work and home-life expectations. Knowledge of the challenges and opportunities presented within the first year of the pandemic can provide a basis for solutions to wicked problems higher education may face in the future.


Association of Catechol-O-Methyl-Transferase and Estrogen Receptors polymorphism with Severity of Temporomandibular Disorder in Iranian Patients.
There are many studies which strongly suggest that the pathophysiology of Temporomandibular joint Disorder (TMD) may also be influenced by genetic conditions. The current study was aimed to evaluate the hypothesis that the polymorphism of estrogen receptor genes, estrogen receptor 1 and 2 (ESR1 and ESR2), and the gene Catechol-O-Methyl-Transferase (COMT) could be Predisposing factor for TMD. In this case-control study, blood sample were taken from 100 TMD diagnosed patients based on Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) and 103 healthy individuals as the control group. Tetra ARMS-PCR method was used to amplify and identify COMT rs4680, ESR1 rs1643821, and ESR2 rs1676303 gene polymorphism. ESR1 genotype AA and GA showed significantly increase probability (OR= 4.80, OR=2.98, respectively) of TMD. ESR2 T/T homozygosity was associated with decreased risk for TMD (OR=0.41). The relationship between COMT and TMD was not statistically significant (p>00.05). The relationship between the severity of TMD and ESR1 was significant (p=0.003). According to the inheritance pattern the COMT and ESR1 gene, in the dominant pattern can be susceptible to TMD and in ESR2 gene, in the recessive pattern can be protective to TMD. It seems that SNPs of ESR1 rs1643821 has a susceptible role and ESR2 rs1676303 has a protective role against TMD. Also, we add evidences that various genotype of COMT rs4680 were not statistically different between case and control, but allele A in the dominant inherence pattern can be susceptible to TMD.


Molecular imaging of antiangiogenic agents.
Many novel antiangiogenic agents are currently in various phases of clinical testing. These agents tend to be cytostatic, and therefore few responses are observed with conventional imaging by computerized tomography. Furthermore, toxicity with these agents is seen when the maximum-tolerated dose is combined with chemotherapy. Hence, there is a need to develop imaging strategies that can determine the minimum and optimum biologically active doses. There is increasing awareness of the need to obtain evidence of drug activity through the use of surrogate markers of the biologic mechanism of action during early clinical trials, in addition to determining the pharmacokinetics, toxicity profile, and maximum-tolerated dose. One of the major impediments to the rapid development of antiangiogenic agents in the past has been the lack of validated assays capable of measuring an antiangiogenic effect directly in patients. Recently, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has emerged as a useful technique for noninvasive imaging of tumor vasculature in preclinical and clinical models. The problem of tumor heterogeneity remains to be addressed. The major challenge is the standardization of the technique worldwide for the purpose of early clinical studies that are likely to be multicenter. Convincing data on correlations between changes observed through molecular imaging and changes in tumor angiogenesis, and hence tumor biology, are still lacking. Whether this would translate into a survival advantage remains to be seen. The ultimate test of the surrogate biological end points determined by molecular imaging will occur in randomized phase III trials. Results of the first randomized trial that showed a survival advantage in favor of antiangiogenic agents were released at the American Society of Clinical Oncology meeting in 2003. There it was reported that the combination of 5-fluorouracil, leucovorin, and irinotecan (Camptosar; Pfizer Pharmaceuticals; New York, NY) with anti-vascular endothelial growth factor antibody (bevacizumab-Avastin; Genentech, Inc.; South San Francisco, CA) was superior to the chemotherapy regimen alone when used to treat patients with metastatic colorectal cancer. However, until further phase III clinical trials confirm these results, surrogate end points of clinical efficacy of the newer agents are urgently needed so that development of ineffective drugs can be halted early. This review briefly discusses the role of molecular imaging in general, and DCE-MRI in particular, in relation to treatment with antiangiogenic agents and highlights some of the difficulties encountered in this area.


The Charles River "hairless" rat mutation is distinct from the hairless mouse alleles.
The Charles River (CR) "hairless" rat is one of the autosomal recessive hypotrichotic animal models actively studied in pharmacologic and dermatologic research. Despite its widespread use, the molecular basis of this monogenic mutation remains unknown, and the skin histologic features of this phenotype have never been described. However, the designation "hairless" has been used as an extension of the hairless mouse (hr) nomenclature on the basis of the clinical absence of hairs in both phenotypes. We present a description of the histopathologic changes in heterozygous and homozygous CR hairless rat mutants during the first month of life. The postnatal homozygous rat skin was characterized by abnormal keratinization of the hair shaft and formation of a thick and dense layer of corneocytes in the lower portion of the epidermal stratum corneum. This layer prevented the improperly keratinized hair shaft from penetrating the skin surface. Starting from the latest stages of hair follicle (HF) development, obvious signs of HF degeneration were observed in homozygous skin. This process was extremely rapid, and by day 12, mainly atrophic HFs with abnormal or broken hairs were present in the skin. Therefore, the mutation in the CR rat abrogates cell proliferation in the hair matrix and affects keratinocyte differentiation in the HF and interfollicular epidermis, a phenotype that is completely distinct from hr/hr. To test whether the CR rat harbored a mutation in the hr gene, we analyzed the coding region of this gene and consensus intron splice site sequences in mutant rats and found no mutation, further supporting phenotypic evidence that the hairless phenotype in CR rats is not allelic with hairless. Finally, using intragenic polymorphisms, we were able to exclude homozygosity at the hairless locus by use of genotypic analysis. Thus, morphologic analysis of successive stages of phenotype development in the CR hairless rat, together with definitive molecular studies, indicate that this mutation may be unique among the other hypotrichotic rat mutations.


Estimating protein-ligand binding affinity using high-throughput screening by NMR.
Many of today's drug discovery programs use high-throughput screening methods that rely on quick evaluations of protein activity to rank potential chemical leads. By monitoring biologically relevant protein-ligand interactions, NMR can provide a means to validate these discovery leads and to optimize the drug discovery process. NMR-based screens typically use a change in chemical shift or line width to detect a protein-ligand interaction. However, the relatively low throughput of current NMR screens and their high demand on sample requirements generally makes it impractical to collect complete binding curves to measure the affinity for each compound in a large and diverse chemical library. As a result, NMR ligand screens are typically limited to identifying candidates that bind to a protein and do not give any estimate of the binding affinity. To address this issue, a methodology has been developed to rank binding affinities for ligands based on NMR screens that use 1D (1)H NMR line-broadening experiments. This method was demonstrated by using it to estimate the dissociation equilibrium constants for twelve ligands with the protein human serum albumin (HSA). The results were found to give good agreement with previous affinities that have been reported for these same ligands with HSA.


Clinicopathologic and Immunophenotypic Classification of Invasive Lobular Carcinoma with Histiocytoid Features.
Histiocytoid lobular breast carcinoma is a rare subtype of invasive lobular carcinoma characterized by relatively bland, uniform nuclei, single small eosinophilic nucleolus, and ample granular cytoplasm. These cancers are typically triple negative, show frequent androgen receptor (AR) positivity, and are therefore theorized to represent a variant of apocrine differentiation in invasive lobular carcinoma. Anecdotal evidence suggests that these tumors have excellent outcomes, though some studies suggest a variable clinical outcome. Inclusion criteria included women with a histologic diagnosis of invasive lobular carcinoma with histiocytoid features, regardless of immunohistochemical profile, diagnosed at our institution between 2008 and 2021 with additional tissue still available for ancillary studies. We reviewed patients meeting these criteria and investigated hematoxylin and eosin-stained slides and a panel of immunohistochemical stains (estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 [HER2], AR, endothelial growth factor receptor, and keratin 5/6), as well as outcomes including survival and metastatic disease. Overall, 12 eligible patients were identified. The classical immunophenotype (triple negative with AR positivity) was noted in 4 out of 12 tumors. The majority of the remaining tumors (7 out of 12) showed a luminal B immunohistochemical profile, while 1 out of 12 was HER2-enriched. No patients in the cohort died from disease-related causes and 2 out of 12 presented with distant metastatic disease during their disease course. Histiocytoid lobular breast carcinoma is a morphologic variant of lobular carcinoma with apocrine features that shows a variable immunohistochemical profile and variable clinical behavior. Further subclassification and stricter diagnostic criteria may be helpful in the distinction between truly indolent tumors and those with more aggressive clinical features.


Quantifying the accuracy of a diagnostic test or marker.
In recent years, increasing focus has been directed to the methodology for evaluating (new) tests or biomarkers. A key step in the evaluation of a diagnostic test is the investigation into its accuracy. We reviewed the literature on how to assess the accuracy of diagnostic tests. Accuracy refers to the amount of agreement between the results of the test under evaluation (index test) and the results of a reference standard or test. The generally recommended approach is to use a prospective cohort design in patients who are suspected of having the disease of interest, in which each individual undergoes the index and same reference standard tests. This approach presents several challenges, including the problems that can arise with the verification of the index test results by the preferred reference standard test, the choice of cutoff value in case of a continuous index test result, and the determination of how to translate accuracy results to recommendations for clinical use. This first in a series of 4 reports presents an overview of the designs of single-test accuracy studies and the concepts of specificity, sensitivity, posterior probabilities (i.e., predictive values) for the presence of target disease, ROC curves, and likelihood ratios, all illustrated with empirical data from a study on the diagnosis of suspected deep venous thrombosis. Limitations of the concept of the diagnostic accuracy for a single test are also highlighted. The prospective cohort design in patients suspected of having the disease of interest is the optimal approach to estimate the accuracy of a diagnostic test. However, the accuracy of a diagnostic index test is not constant but varies across different clinical contexts, disease spectrums, and even patient subgroups.


Uncontrollable hyperthermia in acute cerebral injury: A case report.
A 39 year old man arrived at the hospital with semi-comatose state as a result of spontaneous intracerebral hemorrhage (ICH), intraventricular hemorrhage (IVH) and subarachnoid hemorrhage (SAH). For emergency craniectomy and hematoma removal, general anesthesia with desflurane and vecuronium was planned. Before the induction of anesthesia, the body temperature and end-tidal carbon dioxide (ETCO2) levels were 38.3degrees C and 38 mmHg, respectively. The body temperature and ETCO2 increased during surgery. After 2 hours of anesthesia, the temperature had increased to 41degrees C, despite bladder irrigation and body cooling. After 3 hours of anesthesia, the temperature reached 43.5degrees C and cardiac arrest developed. Cardiopulmonary resuscitation was attempted, but the patient expired.


Vanadate inhibits both intercellular adhesion and spreading on fibronectin of BHK21 cells and transformed derivatives.
Both intercellular adhesion and spreading on fibronectin of BHK21 hamster cells are inhibited by vanadate at concentrations that cause specific regulatory effects rather than general metabolic inhibition. Inhibition of aggregation of these cells in suspension (half-maximal in 10(-5) M vanadate) is rapid and reversible. The extent of inhibition, and its decline with culture age parallel inhibition by agents that depolymerize microtubules. Vanadate also reversibly inhibits spreading of both BHK cells and transformed derivatives on fibronectin. If 10(-4) M vanadate is added to BHK cells that have spread in its absence, they remain spread, but transformed derivatives are sensitive to rounding by vanadate at 10(-6) M. The mechanisms by which vanadate inhibits both intercellular adhesion and spreading are unknown, and may be different for the two phenomena. Possible sensitive targets include cytoplasmic dynein for the former, and protein tyrosyl phosphatase for the latter.


Estradiol inhibits HIV-1BaL infection and induces CFL1 expression in peripheral blood mononuclear cells and endocervical mucosa.
An inhibitory effect of estradiol (E2) on HIV-1 infection was suggested by several reports. We previously identified increased gene expression of actin-binding protein cofilin 1 (CFL1) in endocervix in the E2-dominated proliferative phase of the menstrual cycle. Actin cytoskeleton has an integral role in establishing and spreading HIV-1 infection. Herein, we studied in vitro effects of E2 on HIV-1 infection and on CFL1 expression to gain insight into the mechanism of HIV-1 inhibition by E2. E2 dose-dependently inhibited HIV-1BaL infection in peripheral blood mononuclear cells (PBMCs) and endocervix. In PBMCs and endocervix, E2 increased protein expression of total CFL1 and phosphorylated CFL1 (pCFL1) and pCFL1/CFL1 ratios. LIMKi3, a LIM kinase 1 and 2 inhibitor, abrogated the phenotype and restored infection in both PBMCs and endocervix; inhibited E2-induced expression of total CFL1, pCFL1; and decreased pCFL1/CFL1 ratios. Knockdown of CFL1 in PBMCs also abrogated the phenotype and partially restored infection. Additional analysis of soluble mediators revealed decreased concentrations of pro-inflammatory chemokines CXCL10 and CCL5 in infected tissues incubated with E2. Our results suggest a link between E2-mediated anti-HIV-1 activity and expression of CFL1 in PBMCs and endocervical mucosa. The data support exploration of cytoskeletal signaling pathway targets for the development of prevention strategies against HIV-1.


Bacteria-host cell interaction mediated by cellular cholesterol/glycolipid-enriched microdomains.
Gram negative bacterial infection is a leading cause of fatality and is attributed, at least in part, to the bacteria's capacity to persist in the host in spite of appropriate antibiotic therapy. It has been suggested that bacteria evade antibiotics by hiding within host cells. We sought to investigate this important aspect of infections in mast cells, which are inflammatory cells found in close proximity to the host-environment interface and which have recently been reported to play a crucial role in the early innate immune response to bacteria. We examined mast cell interactions with FimH-expressing E. coli, one of the major opportunistic pathogens of humans. We determined that in serum free conditions, these bacteria were able to trigger mast cell uptake without loss of bacterial viability. CD48, a mannose containing GPI (glycosylphosphatidylinositol)-linked molecule was found to be the receptor of FimH-expressing E. coli in mouse mast cells. We found that the internalization via CD48 was blocked by filipin, a cholesterol binding drug known to disrupt cholesterol/glycolipid-enriched microdomains and the bacteria-encasing vacuoles were rich in cholesterol inside cells. Interestingly, we found that mast cells subsequently expelled majority of the intracellular bacteria in 24 hours. This expulsion process was blocked by lovastatin/cyclodextrin treatment, which is known to inhibit cellular trafficking of cholesterol/glycolipid-enriched microdomains. Thus, the bacterial entry into and expulsion from mast cells were critically dependent on cholesterol/glycolipid-enriched microdomains, which represents a novel mode of tussle between the pathogen and the mast cell occurring in opsonin deficient sites in the body or even at other sites in naive or immunocompromised hosts which have low systemic levels of E. coli specific antibody.


Appearance-Based Gaze Estimation via Uncalibrated Gaze Pattern Recovery.
Aiming at reducing the restrictions due to person/scene dependence, we deliver a novel method that solves appearance-based gaze estimation in a novel fashion. First, we introduce and solve an "uncalibrated gaze pattern" solely from eye images independent of the person and scene. The gaze pattern recovers gaze movements up to only scaling and translation ambiguities, via nonlinear dimension reduction and pixel motion analysis, while no training/calibration is needed. This is new in the literature and enables novel applications. Second, our method allows simple calibrations to align the gaze pattern to any gaze target. This is much simpler than conventional calibrations which rely on sufficient training data to compute person and scene-specific nonlinear gaze mappings. Through various evaluations, we show that: 1) the proposed uncalibrated gaze pattern has novel and broad capabilities; 2) the proposed calibration is simple and efficient, and can be even omitted in some scenarios; and 3) quantitative evaluations produce promising results under various conditions.


Role of self-care in the patient with heart failure.
Optimal outcomes and quality of life for patients with heart failure depend on engagement in effective self-care activities. Self-care is a complex set of activities and most clinicians are not adequately prepared to assist their patients to engage in effective self-care. In this paper, we provide an overview of self-care that includes definitions, the importance of self-care to outcomes, the physiologic basis for better outcomes with good self-care, cultural perspectives of self-care, and recommendations for the improvement of self-care. Promotion of effective self-care by all clinicians could substantially reduce the economic and personal burden of repeated rehospitalizations among patients with heart failure.


Methiothepin downregulates SNAP-23 and inhibits degranulation of rat basophilic leukemia cells and mouse bone marrow-derived mast cells.
In the present study, we found that methiothepin (a nonselective 5-hydroxytryptamine [5-HT] receptor antagonist) inhibited antigen-induced degranulation in rat basophilic leukemia cells and mouse bone marrow-derived mast cells. Although antigen stimulation induces release of histamine and serotonin (5-HT) by exocytosis and mast cells express several types of 5-HT receptor, the detailed role of these receptors remains unclear. Here, pretreatment of cells with methiothepin attenuated increased intracellular Ca2+ concentration, phosphorylated critical upstream signaling components (Src family tyrosine kinases, Syk, and PLCγ1), and suppressed TNF-α secretion via inhibition of Akt (a Ser/Thr kinase activated by PI3K)and ERK phosphorylation. Furthermore, it inhibited PMA/ionomycin-induced degranulation; this finding suggested that methiothepin affected downstream signaling. IκB kinase β phosphorylates synaptosomal associated protein 23, which regulates the fusion events of the secretory granule/plasma membrane after mast cell activation, resulting in degranulation. We showed that methiothepin blocked PMA/ionomycin-induced phosphorylation of synaptosomal associated protein 23 by inhibiting its interaction with IκB kinase β. Together with the results of selective 5-HT antagonists, it is suggested that methiothepin inhibits mast cell degranulation by downregulating upstream signaling pathways and exocytotic fusion machinery through mainly 5-HT1A receptor. Our findings provide that 5-HT antagonists may be used to relieve allergic reactions.


Association between depression and functional vision loss in persons 20 years of age or older in the United States, NHANES 2005-2008.
This study provides further evidence from a national sample to generalize the relationship between depression and vision loss to adults across the age spectrum. Better recognition of depression among people reporting reduced ability to perform routine activities of daily living due to vision loss is warranted. To estimate, in a national survey of US adults 20 years of age or older, the prevalence of depression among adults reporting visual function loss and among those with visual acuity impairment. The relationship between depression and vision loss has not been reported in a nationally representative sample of US adults. Previous studies have been limited to specific cohorts and predominantly focused on the older population. The National Health and Nutrition Examination Survey (NHANES) 2005-2008. A cross-sectional, nationally representative sample of adults, with prevalence estimates weighted to represent the civilian, noninstitutionalized US population. A total of 10 480 US adults 20 years of age or older. Depression, as measured by the 9-item Patient Health Questionnaire depression scale, and vision loss, as measured by visual function using a questionnaire and by visual acuity at examination. In 2005-2008, the estimated crude prevalence of depression (9-item Patient Health Questionnaire score of ≥10) was 11.3% (95% CI, 9.7%-13.2%) among adults with self-reported visual function loss and 4.8% (95% CI, 4.0%-5.7%) among adults without. The estimated prevalence of depression was 10.7% (95% CI, 8.0%-14.3%) among adults with presenting visual acuity impairment (visual acuity worse than 20/40 in the better-seeing eye) compared with 6.8% (95% CI, 5.8%-7.8%) among adults with normal visual acuity. After controlling for age, sex, race/ethnicity, marital status, living alone or not, education, income, employment status, health insurance, body mass index, smoking, binge drinking, general health status, eyesight worry, and major chronic conditions, self-reported visual function loss remained significantly associated with depression (overall odds ratio, 1.9 [95% CI, 1.6-2.3]), whereas the association between presenting visual acuity impairment and depression was no longer statistically significant. Self-reported visual function loss, rather than loss of visual acuity, is significantly associated with depression. Health professionals should be aware of the risk of depression among persons reporting visual function loss.


Effects of varying forage particle size and fermentable carbohydrates on feed sorting, ruminal fermentation, and milk and component yields of dairy cows.
Ration sorting is thought to affect ruminal fermentation in such a manner that milk yield milk and components are often decreased. However, the influence of ruminally degradable starch on ration sorting has not been studied. Therefore, the objective of this experiment was to evaluate the interactions between forage particle size (FPS) and ruminally fermentable carbohydrates (RFC) for dry matter intake (DMI), ration sorting, ruminal fermentation, chewing activity, and milk yield and components. In this study, 12 (8 ruminally cannulated) multiparous, lactating Holstein cows were fed a total mixed ration that varied in FPS and RFC. Two lengths of corn silage were used to alter FPS and 2 grind sizes of corn grain were used to alter RFC. It was determined that increasing RFC increased ruminating time and did not affect eating time, whereas increasing FPS increased eating time and did not affect ruminating time. Ruminal fermentation did not differ by altering either FPS or RFC. However, increasing FPS tended to increase mean and maximum ruminal pH and increasing RFC tended to decrease minimum ruminal pH. Particle size distribution became more diverse and neutral detergent fiber content of refusals increased over time, whereas starch content decreased, indicating that cows were sorting against physically effective neutral detergent fiber and for RFC. Selection indices determined that virtually no interactions occurred between FPS and RFC and that despite significant sorting throughout the day, by 24h after feeding cows had consumed a ration very similar to what was offered. This theory was reinforced by particle fraction intakes that very closely resembled the proportions of particle fractions in the offered total mixed ration. An interaction between FPS and RFC was observed for DMI, as DMI decreased with increasing FPS when the diet included low RFC and did not change when the diet included high RFC. Dry matter intake increased with RFC for long diets and did not change with RFC on short diets. Increasing RFC was found to increase milk yield, milk protein content and yield, and lactose content and yield but decrease milk fat content. Increasing FPS did not have as great an effect on milk production as RFC. This study found no significant interaction between FPS and RFC for ration sorting, although an interaction between FPS and RFC for DMI was observed. Neither FPS nor RFC affected ruminal fermentation, whereas RFC had a greater influence on milk yield and components than FPS.


Four distinct secretory pathways serve protein secretion, cell surface growth, and peroxisome biogenesis in the yeast Yarrowia lipolytica.
We have identified and characterized mutants of the yeast Yarrowia lipolytica that are deficient in protein secretion, in the ability to undergo dimorphic transition from the yeast to the mycelial form, and in peroxisome biogenesis. Mutations in the SEC238, SRP54, PEX1, PEX2, PEX6, and PEX9 genes affect protein secretion, prevent the exit of the precursor form of alkaline extracellular protease from the endoplasmic reticulum, and compromise peroxisome biogenesis. The mutants sec238A, srp54KO, pex2KO, pex6KO, and pex9KO are also deficient in the dimorphic transition from the yeast to the mycelial form and are affected in the export of only plasma membrane and cell wall-associated proteins specific for the mycelial form. Mutations in the SEC238, SRP54, PEX1, and PEX6 genes prevent or significantly delay the exit of two peroxisomal membrane proteins, Pex2p and Pex16p, from the endoplasmic reticulum en route to the peroxisomal membrane. Mutations in the PEX5, PEX16, and PEX17 genes, which have previously been shown to be essential for peroxisome biogenesis, affect the export of plasma membrane and cell wall-associated proteins specific for the mycelial form but do not impair exit from the endoplasmic reticulum of either Pex2p and Pex16p or of proteins destined for secretion. Biochemical analyses of these mutants provide evidence for the existence of four distinct secretory pathways that serve to deliver proteins for secretion, plasma membrane and cell wall synthesis during yeast and mycelial modes of growth, and peroxisome biogenesis. At least two of these secretory pathways, which are involved in the export of proteins to the external medium and in the delivery of proteins for assembly of the peroxisomal membrane, diverge at the level of the endoplasmic reticulum.


Rationale for the revision of oxytocin administration protocols.
A physiologic rationale, based on a review of the literature, is provided for implementing a protocol for labor induction or augmentation with intravenous oxytocin infusion. Oxytocin dosage should simulate the amount normally released endogenously during labor. Recent studies suggest that smaller dose regimens are as effective as previous larger dose regimens and that adverse effects of oxytocin are dose related. Nurses must know the relationship between the physiology of normal labor and the pharmacokinetics and safe administration of oxytocin during labor.


(De)Politicizing Polyamory: Social Media Comments on Media Representations of Consensual Non-Monogamies.
Our research sits at the intersection of communication studies, sociology, cyberculture, and political philosophy and theory. In 2014, a 10+-min segment on polyamory aired on Portuguese open-access national television, during the prime-time newscast, and was viewed by several million people, according to official reports. The news piece was also advertised and shared online, especially via Facebook, by the network's official page. Moreover, the piece was aired within the context of a segment that celebrated the 40-year anniversary of the 1974 liberal revolution that overthrew the right-wing dictatorial regime that ruled Portugal for more than half of the twentieth century. This context served to frame polyamory (alongside other topics) as explicitly political by presenting them as freedoms seized by that liberal revolution. This study used a mixed-method approach to the analysis of online comments on Facebook made with respect to the referred news piece, by deploying both content analysis and critical discourse analysis to try to understand how the political nature of polyamory is negotiated (affirmed or disavowed), and what ideal of the "political" is mobilized in that negotiation, in connection with other elements of intimate citizenship and modes of systemic discrimination. Through this analysis, we will deepen our understanding of how lay people construe the "political" and the (non-)politicalness of polyamory. It also helps advance contemporary understandings of how polyamory is represented in mainstream media, understood by audiences, and how media-and debates on online social networks-can both amplify and help fight against harmful stereotypes of minorities. Through this research, we contribute to political theory by opening up new ways of conceptualizing the realm of the political as an open-ended definition that must encompass changes in modes of sociality, including a politics of relating as a sub-field, likewise to the study of social movements, and their strategies, around consensual non-monogamies. Overall, results show that the recognition of the validity of polyamory is not the same as the realization that relationship orientation is a political issue in itself and that a privatized mode of understanding politics seems prevalent as well as the default framework used in the comments we analyzed. In addition to that, and as other research has already noted, incivility and hate speech was prevalent in online comments and discussions, further dampening the political potential of dissident modes of existence, especially given that incivility is also deployed by those speaking in favor of Othered identities and experiences.


[Mechanism of changes in the rate of glycolysis and levels of ATP and 2,3-diphosphoglycerate in human erythrocytes during aging].
Reasons which have induced changes in the glycolysis rate, ATP and 2,3-diphosphoglycerate content in human erythrocytes with ageing are studied. A fall of the hexokinase activity is shown to be one of the reasons of a significant decrease in the glycolysis rate. The total ATPase activity in erythrocytes does not change with the age. At the same time the decay rate of 2,3-diphosphoglycerate increases, that, evidently, is one of the reasons of the 2,3-diphosphoglycerate content decrease in erythrocytes with ageing.


Surgical management of patients with Marfan syndrome: evolution throughout the years.
To evaluate the evolution of surgical management in a large population of patients with Marfan syndrome. This is a retrospective study of patients fulfilling the Ghent criteria for Marfan syndrome, who visited the Centre de référence national pour le syndrome de Marfan et apparentés and underwent a surgical event before or during follow-up in the centre. One thousand and ninety-seven patients with Marfan syndrome, according to international criteria, came to the clinic between 1996 and 2010. Aortic surgery was performed in 249 patients (22.7%; 20 children and 229 adults), including the Bentall procedure in 140 patients (56%) and valve-sparing surgery in 88 patients (35%); a supracoronary graft was performed in 19 patients (7.6%), usually for aortic dissection. During the past 20 years, the predominant reason for aortic surgery has switched from aortic dissection to aortic dilatation, while age at surgery has tended to increase (from 32.4 ± 11.9 years to 35.2 ± 12.4 years; P=0.075). Mitral valve surgery was performed in 61 patients (5.6%; six children and 55 adults), including 37 valvuloplasties (60.6%) and 18 mitral valve replacements (29.5%). No significant difference was observed when comparing mitral valve surgery before and after 2000. Surgery performed in patients with Marfan syndrome has switched from emergency surgery for aortic dissection to elective surgery for aortic dilatation; this is associated with surgery performed at an older age despite the indication for surgery having decreased from 60mm to 50mm. No significant evolution was observed for mitral valve surgery.


Secreted ectodomain of sialic acid-binding Ig-like lectin-9 and monocyte chemoattractant protein-1 promote recovery after rat spinal cord injury by altering macrophage polarity.
Engrafted mesenchymal stem cells from human deciduous dental pulp (SHEDs) support recovery from neural insults via paracrine mechanisms that are poorly understood. Here we show that the conditioned serum-free medium (CM) from SHEDs, administered intrathecally into rat injured spinal cord during the acute postinjury period, caused remarkable functional recovery. The ability of SHED-CM to induce recovery was associated with an immunoregulatory activity that induced anti-inflammatory M2-like macrophages. Secretome analysis of the SHED-CM revealed a previously unrecognized set of inducers for anti-inflammatory M2-like macrophages: monocyte chemoattractant protein-1 (MCP-1) and the secreted ectodomain of sialic acid-binding Ig-like lectin-9 (ED-Siglec-9). Depleting MCP-1 and ED-Siglec-9 from the SHED-CM prominently reduced its ability to induce M2-like macrophages and to promote functional recovery after spinal cord injury (SCI). The combination of MCP-1 and ED-Siglec-9 synergistically promoted the M2-like differentiation of bone marrow-derived macrophages in vitro, and this effect was abolished by a selective antagonist for CC chemokine receptor 2 (CCR2) or by the genetic knock-out of CCR2. Furthermore, MCP-1 and ED-Siglec-9 administration into the injured spinal cord induced M2-like macrophages and led to a marked recovery of hindlimb locomotor function after SCI. The inhibition of this M2 induction through the inactivation of CCR2 function abolished the therapeutic effects of both SHED-CM and MCP-1/ED-Siglec-9. Macrophages activated by MCP-1 and ED-Siglec-9 extended neurite and suppressed apoptosis of primary cerebellar granule neurons against the neurotoxic effects of chondroitin sulfate proteoglycans. Our data suggest that the unique combination of MCP-1 and ED-Siglec-9 repairs the SCI through anti-inflammatory M2-like macrophage induction.


Pazopanib for the treatment of renal cancer.
Dramatic advances in the care of patients with advanced renal cell carcinoma (RCC) have occurred over the last 10 years. Insights into the molecular pathogenesis of this disease have elucidated the importance of signaling cascades related to angiogenesis in the management of RCC. Pazopanib is a novel, small-molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptors (VEGFR)-1, -2, and -3; platelet-derived growth factor receptors (PDGFR)-α and -β; and c-kit tyrosine kinases. Pazopanib exhibits distinct pharmacokinetic and toxicity profiles compared with other agents in the class of VEGF signaling pathway inhibitors. This review discusses the scientific rationale for the development of pazopanib, as well as the preclinical and clinical trials that led to the approval of pazopanib for patients with advanced RCC. The most recent information, including data from the 2010 meeting of the American Society of Clinical Oncology and the design of ongoing Phase III trials, is discussed. Finally, an algorithm utilizing level I evidence for the treatment of patients with this disease is proposed. The treatment of metastatic RCC has changed dramatically over the last 5 years. Six novel agents - sunitinib, sorafenib, temsirolimus, everolimus, bevacizumab (used in combination with interferon), and pazopanib (Votrient) - have been approved for the treatment of metastatic RCC. The clinical data to date clearly place pazopanib among the most active of the targeted therapies.


Assessment of Hygiene Habits in Acrylic Denture Wearers: a Cross-sectional Study.
To assess the denture hygiene habits in a population of Lebanese denture wearers. One hundred and thirty-two (132) patients [71 women (53.8%) and 61 men (46.2%)] wearing their acrylic dentures for more than two years were included in this study. The hygiene methods related to their dentures were evaluated and the data obtained were analyzed statistically using the IBM® SPSS® statistics 20.0 (USA) statistical package. Regardless of the cleaning technique, the big majority of our participants [123 out of 132 (93.1%)] cleaned their dentures daily. The two mostly used denture cleaning techniques were rinsing with tap water (34.1%) and brushing with toothpaste (31.8%). Nearly half of our patients (45.5%) soaked their dentures during the night; most of them with cleansing tablets dissolved in water (28.8%). Within the limitations of our study, it was concluded that in a sample of Lebanese population surveyed about denture hygiene habits, the daily frequency of denture cleaning is satisfactory, but the techniques and products used were self-estimated and, consequently, not sufficient.


Anti-Carcinogenic Effects of Carnosol-An Updated Review.
Despite the newly treatment procedures, cancer is considered as the main health threat nowadays and, therefore, new therapeutic options such as traditional medicine should be investigated. Rosemary (Rosmarinus officinalis L.) has been found to possess antitumor effects due to its major ingredients, including carnosic acid, carnosol, ursolic acid, and rosmarinic acid. This study was designed to gather the recent literature findings from 2010 to 2016 on the cancer anti-tumor activities of carnosol and probably involved mechanisms. The online English papers were gathered through various search websites, including PubMed, Iran Medex, Medline, Google Scholar, and Scopus from 2010 to 2016. Carnosol, the specific composition of rosemary, has been shown to have beneficial effects in keeping humans healthy and may be acted as an antitumor agent. This review revealed that carnosol may be effective as an anti-tumor agent in the different types of cancer by inducing apoptosis and inhibiting the cell cycle division. However, more studies are needed to confirm carnosol therapeutic effects in human.


A chicken caudal homologue, CHox-cad, is expressed in the epiblast with posterior localization and in the early endodermal lineage.
CHox-cad is a chicken homeobox gene whose homeodomain is homologous to the Drosophila caudal and the murine Cdx1 genes. Based on sequence analysis of a 2.5 kb CHox-cad cDNA clone, we deduced that the primary translation product consists of 248 amino acids. Comparison between the cDNA and genomic clones revealed the presence of an intron within the CHox-cad homeodomain between amino acids 44 and 45. The onset of CHox-cad transcription correlates temporarily with the beginning of gastrulation. During primitive streak stages CHox-cad exhibits a caudally localized pattern of expression restricted to the epiblast and the primitive streak. At these stages, CHox-cad transcripts can also be detected in the definitive endoderm cells. Later in embryogenesis CHox-cad is expressed in the epithelial lining of the embryonic gut and yolk sac. After four days of chicken development, no CHox-cad transcripts could be detected. The early CHox-cad posterior expression in the germ layer undergoing gastrulation and its continuous expression in the early endodermal lineage raise the possibility of CHox-cad involvement in the establishment of the definitive endoderm.


HIV-1 vaccine-induced T-cell responses cluster in epitope hotspots that differ from those induced in natural infection with HIV-1.
Several recent large clinical trials evaluated HIV vaccine candidates that were based on recombinant adenovirus serotype 5 (rAd-5) vectors expressing HIV-derived antigens. These vaccines primarily elicited T-cell responses, which are known to be critical for controlling HIV infection. In the current study, we present a meta-analysis of epitope mapping data from 177 participants in three clinical trials that tested two different HIV vaccines: MRKAd-5 HIV and VRC-HIVAD014-00VP. We characterized the population-level epitope responses in these trials by generating population-based epitope maps, and also designed such maps using a large cohort of 372 naturally infected individuals. We used these maps to address several questions: (1) Are vaccine-induced responses randomly distributed across vaccine inserts, or do they cluster into immunodominant epitope hotspots? (2) Are the immunodominance patterns observed for these two vaccines in three vaccine trials different from one another? (3) Do vaccine-induced hotspots overlap with epitope hotspots induced by chronic natural infection with HIV-1? (4) Do immunodominant hotspots target evolutionarily conserved regions of the HIV genome? (5) Can epitope prediction methods be used to identify these hotspots? We found that vaccine responses clustered into epitope hotspots in all three vaccine trials and some of these hotspots were not observed in chronic natural infection. We also found significant differences between the immunodominance patterns generated in each trial, even comparing two trials that tested the same vaccine in different populations. Some of the vaccine-induced immunodominant hotspots were located in highly variable regions of the HIV genome, and this was more evident for the MRKAd-5 HIV vaccine. Finally, we found that epitope prediction methods can partially predict the location of vaccine-induced epitope hotspots. Our findings have implications for vaccine design and suggest a framework by which different vaccine candidates can be compared in early phases of evaluation.


Evaluation of preterm delivery in a systemic lupus erythematosus pregnancy clinic.
To identify the primary etiology of preterm birth in women with systemic lupus erythematosus, analyzing prospective data collected on 66 pregnancies in 58 women followed-up at a lupus pregnancy center. Hospital records were reviewed and subjects were interviewed for pregnancies delivered after 23 completed weeks' gestation in women cared for at the Hopkins Lupus Pregnancy Center. A control group consisted of all women delivered at the same hospital during 2 years of the study period. Preterm premature rupture of membranes (PROM) occurred in 13 of 33 (39%) pregnancies delivered at 24-36 weeks' gestation. In addition, term PROM also occurred with high incidence in ten of 33 (30.3%) pregnancies delivered after 36 weeks' gestation. The rate of PROM in study subjects differed from that in controls at 34-36 weeks' gestation and after 36 weeks. Premature rupture of membranes is more common in pregnancies occurring in women with systemic lupus erythematosus than in control pregnancies. Disease activity, prednisone use, and serologic studies are not predictive. Premature rupture of membranes is the major etiology of preterm birth in this cohort.


Demography and rapid local adaptation shape Creole cattle genome diversity in the tropics.
The introduction of Iberian cattle in the Americas after Columbus' arrival imposed high selection pressures on a limited number of animals over a brief period of time. Knowledge of the genomic regions selected during this process may help in enhancing climatic resilience and sustainable animal production. We first determined taurine and indicine contributions to the genomic structure of modern Creole cattle. Second, we inferred their demographic history using approximate Bayesian computation (ABC), linkage disequilibrium (LD) and N e Slope (NeS) analysis. Third, we performed whole genome scans for selection signatures based on cross-population extended haplotype homozygosity (XP-EHH) and population differentiation (F ST) to disentangle the genetic mechanisms involved in adaptation and phenotypic change by a rapid and major environmental transition. To tackle these questions, we combined SNP array data (~54,000 SNPs) in Creole breeds with their modern putative Iberian ancestors. Reconstruction of the population history of Creoles from the end of the 15th century indicated a major demographic expansion until the introduction of zebu and commercial breeds into the Americas ~180 years ago, coinciding with a drastic N e contraction. NeS analysis provided insights into short-term complexity in population change and depicted a decrease/expansion episode at the end of the ABC-inferred expansion, as well as several additional fluctuations in N e with the attainment of the current small N e only towards the end of the 20th century. Selection signatures for tropical adaptation pinpointed the thermoregulatory slick hair coat region, identifying a new candidate gene (GDNF), as well as novel candidate regions involved in immune function, behavioural processes, iron metabolism and adaptation to new feeding conditions. The outcomes from this study will help in future-proofing farm animal genetic resources (FAnGR) by providing molecular tools that allow selection for improved cattle performance, resilience and welfare under climate change.


Pivotal results for the Medtronic Valiant Thoracic Stent Graft System in the VALOR II trial.
We report 30-day and 12-month results of endovascular treatment with the Valiant Thoracic Stent Graft System (Medtronic Vascular, Santa Rosa, Calif) in patients with descending thoracic aortic aneurysms of degenerative etiology. The Valiant stent graft is an evolution of the Talent thoracic stent graft (Medtronic Vascular). The VALOR II (Evaluation of the Clinical Performance of the Valiant Thoracic Stent Graft System in the Treatment of Descending Thoracic Aneurysms of Degenerative Etiology in Subjects Who Are Candidates for Endovascular Repair) was a prospective, nonrandomized, pivotal trial conducted at 24 U.S. sites with enrollment between December 2006 and September 2009. Standard follow-up examinations, including physical examination, computed tomography, and chest radiography, were at 1, 6, and 12 months, and annually through 5 years. VALOR II outcomes were compared with those from the pivotal VALOR (Evaluation of the Medtronic Vascular Talent Thoracic Stent Graft System for the Treatment of Thoracic Aortic Aneurysms) trial of the Talent stent graft, which enrolled 195 patients with similar enrollment criteria. VALOR II enrolled 160 patients. Compared with VALOR patients, VALOR II patients had similar age and sex distribution but higher rates of cardiovascular risk factors and significantly more severe modified Society for Vascular Surgery/American Association for Vascular Surgery risk scores. Stent graft delivery and deployment were successful in 154 patients (96.3%). Outcomes at 30 days in VALOR II were perioperative mortality, 3.1%; major adverse events, 38.1%; paraplegia, 0.6%; paraparesis, 1.9%; and stroke, 2.5%. At 12 months, after the minimum sample size was reached, 151 patients were evaluated: aneurysm-related mortality was 4.0%, stent graft migration was 2.9%, and endoleak was 13.0%. Through 12 months, there were no ruptures, conversions to open surgery, secondary procedures due to endoleak >30 days, or loss of stent graft patency. The Valiant stent graft was statistically noninferior to the Talent stent graft in 12-month all-cause mortality (12.6% vs 16.1%) and exceeded the primary effectiveness goal of 12-month successful aneurysm treatment, defined as absence of aneurysm growth >5 mm and of secondary procedures for type I/III endoleak (97.4% vs 80.0%). The VALOR II 12-month results demonstrate that the Medtronic Valiant thoracic stent graft is a safe and effective treatment for patients with descending thoracic aortic aneurysms of degenerative etiology.


Digital Self-monitoring of Multiple Sclerosis: Interview Study With Dutch Health Care Providers on the Expected New Configuration of Roles and Responsibilities.
Digital self-monitoring allows patients to produce and share personal health data collected at home. This creates a novel situation in which health care providers and patients must engage in a reconfiguration of roles and responsibilities. Although existing research pays considerable attention to the perceptions of patients regarding digital self-monitoring, less attention has been paid to the needs, wishes, and concerns of health care providers. As several companies and public institutions are developing and testing digital self-monitoring at the time of writing, it is timely and relevant to explore how health care providers envision using these technologies in their daily work practices. Our findings can be considered in decision-making processes concerning the further development and implementation of digital self-monitoring. This study aims to explore how health care providers envisage using smartphone apps for digital self-monitoring of multiple sclerosis (MS) in their daily work practices, with a particular focus on physician-patient communication and on how health care providers respond to self-monitoring data and delegate tasks and responsibilities to patients. We conducted semistructured in-depth interviews with 14 MS health care providers: 4 neurologists, 7 MS specialist nurses, and 3 rehabilitation professionals. They are affiliated with 3 different hospitals in the Netherlands that will participate in a pilot study to assess the efficiency and effectiveness of a specific smartphone app for self-monitoring. The interviewed health care providers seemed willing to use these smartphone apps and valued the quantitative data they produce that can complement the narratives that patients provide during medical appointments. The health care providers primarily want to use digital self-monitoring via prescription, meaning that they want a standardized smartphone app and want to act as its gatekeepers. Furthermore, they envisioned delegating particular tasks and responsibilities to patients via digital self-monitoring, such as sharing data with the health care providers or acting on the data, if necessary. The health care providers expected patients to become more proactive in the management of their disease. However, they also acknowledged that not all patients are willing or able to use digital self-monitoring apps and were concerned about the potential psychological and emotional burden on patients caused by this technology. Our findings show that health care providers envisage a particular type of patient empowerment and personalized health care in which tensions arise between health care providers acting as gatekeepers and patient autonomy, between patient empowerment and patient disempowerment, and between the weight given to quantitative objective data and that given to patients' subjective experiences. In future research, it would be very interesting to investigate the actual experiences of health care providers with regard to digital self-monitoring to ascertain how the tensions mentioned in this paper play out in practice.


TEACH Cards: Teaching Evidence-Based Medicine and Clinical Topics in the Hospital.
Inpatient training and evidence-based medicine (EBM) curricula are fundamental components of medical education. Teaching EBM And Clinical topics in the Hospital (TEACH) Cards is an inpatient curricular tool developed to help guide efficient, discussion-based teaching sessions. TEACH Cards aims to increase frequency of inpatient teaching, improve exposure to the breadth of inpatient topics, advance EBM skills, and improve efficiency in answering clinical questions. TEACH Cards is a set of 25 topic-based cards, each addressing an adult inpatient medicine topic by asking background questions and encouraging learners to write and answer foreground questions. Residents and faculty from a family medicine residency rotating on an adult inpatient medicine service during the 6-month study period were invited to complete a prerotation survey, use the TEACH Cards, and then complete a postrotation survey. Out of 54 potential participants, 35% completed both the pre- and postrotation surveys. Respondents used TEACH Cards on average three times per week, reporting significantly stronger agreement that they were both learning (P=0.034) and teaching (P=0.006) core inpatient topics. Respondents reported greater confidence in using EBM resources ( P=0.006) and significantly shorter time to find an evidence-based answer to a clinical question (pretest median=6-10 minutes vs posttest median=2-5 minutes, P=0.002). Use of TEACH Cards increased self-reported exposure to the breadth of core inpatient topics, confidence with EBM skills, and efficiency in finding answers to clinical questions.


HbA1c and risk of severe hypoglycemia in type 2 diabetes: the Diabetes and Aging Study.
We examined the association between HbA1c level and self-reported severe hypoglycemia in patients with type 2 diabetes. Type 2 diabetic patients in a large, integrated healthcare system, who were 30-77 years of age and treated with glucose-lowering therapy, were asked about severe hypoglycemia requiring assistance in the year prior to the Diabetes Study of Northern California survey conducted in 2005-2006 (62% response rate). The main exposure of interest was the last HbA1c level collected in the year preceding the observation period. Poisson regression models adjusted for selected demographic and clinical variables were specified to evaluate the relative risk (RR) of severe hypoglycemia across HbA1c levels. We also tested whether the HbA1c-hypoglycemia association differed across potential effect modifiers (age, diabetes duration, and category of diabetes medication). Among 9,094 eligible survey respondents (mean age 59.5 ± 9.8 years, mean HbA1c 7.5 ± 1.5%), 985 (10.8%) reported experiencing severe hypoglycemia. Across HbA1c levels, rates of hypoglycemia were 9.3-13.8%. Compared with those with HbA1c of 7-7.9%, the RR of hypoglycemia was 1.25 (95% CI 0.99-1.57), 1.01 (0.87-1.18), 0.99 (0.82-1.20), and 1.16 (0.97-1.38) among those with HbA1c <6, 6-6.9, 8-8.9, and ≥9%, respectively, in a fully adjusted model. Age, diabetes duration, and category of diabetes medication did not significantly modify the HbA1c-hypoglycemia relationship. Severe hypoglycemia was common among patients with type 2 diabetes across all levels of glycemic control. Risk tended to be higher in patients with either near-normal glycemia or very poor glycemic control.


Selective translational regulation of ribosomal protein gene expression during early development of Drosophila melanogaster.
We have previously characterized a cloned cDNA coding for a developmentally regulated mRNA in Drosophila melanogaster whose expression is selectively regulated at the translational level during oogenesis and embryogenesis. In this report we show that this translationally regulated mRNA (rpA1) codes for an acidic ribosomal protein. Furthermore, our results indicate that most ribosomal protein mRNAs are regulated similarly to rpA1 mRNA. This conclusion is based on cell-free translation of mRNAs derived from polysomes and postpolysomal supernatants as well as in vivo labeling experiments. Thus, the translation of many ribosomal protein mRNAs appears to be temporally related to the synthesis of rRNA during D. melanogaster development. The relationship between rRNA transcription and ribosomal protein mRNA translation was further investigated by genetically reducing rRNA synthesis with the use of bobbed mutants. Unexpectedly, neither ribosomal protein mRNA abundance nor translation was altered in these mutants.


Back pain in former intercollegiate rowers. A long-term follow-up study.
Research has shown that 32% of intercollegiate rowers develop back pain during their college career. Rowers who develop back pain in college are more likely than the general population to have back pain later in life. Survey. Surveys from 1561 former intercollegiate rowing athletes were analyzed. Subjects who completed the surveys had graduated from college at a mean and median of 13 years previously, with a range of 0 to 20 years between graduation and completion of the survey. The survey was designed to determine the presence of back pain and its severity before, during, and after intercollegiate rowing. Back pain was defined as pain that lasted at least 1 week. Age was a significant predictor of back pain after college. Nevertheless, the lifetime prevalence of back pain in former intercollegiate rowers was no different from that of the general population (51.4% versus 60% to 80%). However, rowers who developed back pain in college had more subsequent back pain than rowers who were asymptomatic in college (78.9% versus 37.9%). Rowers who were asymptomatic in college had significantly lower rates of back pain as they aged than did the general population. The mean severity of current back pain was 3.5 +/- 1.9 on a scale of 1 to 10. Intercollegiate rowers are no more likely than the general population to have back pain later in life.


Reelin mRNA expression during mouse brain development.
Using in situ hybridization, expression of the mRNA for reelin, the gene most probably responsible for the reeler trait, was studied during mouse brain development, from embryonic day 13 to maturity. The highest level of expression was found in Cajal-Retzius neurons, while a high signal was also seen in the olfactory bulb, the external granular layer of the cerebellum and, particularly at early developmental stages, in hypothalamic differentiation fields, tectum and spinal cord. A moderate to low level of expression was found in the septal area, striatal fields, habenular nuclei, some thalamic nuclei, particularly the lateral geniculate, the retina and some nuclei of the reticular formation in the central field of the medulla. Paradoxically, no reelin expression was detected in radial glial cells, the cortical plate, Purkinje cells, inferior olivary neurons and many other areas that are characteristically abnormal in reeler mutant mice. Together with other preliminary studies, the present observations suggest that the action of reelin is indirect, possibly mediated by the extracellular matrix. Most of the data can be explained by supposing that reelin is a cell-repulsive molecule which prevents migrating neurons from invading reelin-rich areas, and thus facilitates the deployment of radial glial cell processes and the formation of early architectonic patterns.


Stopping the error cascade: a report on ameliorators from the ASIPS collaborative.
To present a novel examination of how error cascades are stopped (ameliorated) before they affect patients. Qualitative analysis of reported errors in primary care. Over a three-year period, clinicians and staff in two practice-based research networks voluntarily reported medical errors to a primary care patient safety reporting system, Applied Strategies for Improving Patient Safety (ASIPS). The authors found a number of reports where the error was corrected before it had an adverse impact on the patient. Of 754 codeable reported events, 60 were classified as ameliorated events. In these events, a participant stopped the progression of the event before it reached or affected the patient. Ameliorators included doctors, nurses, pharmacists, diagnostic laboratories and office staff. Additionally, patients or family members may be ameliorators by recognising the error and taking action. Ameliorating an event after an initial error requires an opportunity to catch the error by systems, chance or attentiveness. Correcting the error before it affects the patient requires action either directed by protocols and systems or by vigilance, power to change course and perseverance on the part of the ameliorator. Despite numerous individual and systematic methods to prevent errors, a system to prevent all potential errors is not feasible. However, a more pervasive culture of safety that builds on simple acts in addition to more costly and complex electronic systems may improve patient outcomes. Medical staff and patients who are encouraged to be vigilant, ask questions and seek solutions may correct otherwise inevitable wrongs.


The molecular mechanism of the inhibition effects of PVCaps on the growth of sI hydrate: an unstable adsorption mechanism.
The inhibition properties of kinetic hydrate inhibitor (KHI) molecules on the dynamic growth of a hydrate/water interface are investigated by using molecular dynamics simulations. The shape of the hydrate interface is transformed from laminar to funnel by PVCaps. Results indicate that the inhibition effects not only depend on the adsorption capacity which was believed to determine inhibition, but also on the fact that PVCaps must have some non-binding-hydrate sites that don't tend to combine with hydrate. By observing the time evolution of the distance between each component of PVCaps and hydrate, the heterocyclic ring of PVCaps mainly contributes to adsorption and can preferentially adjust itself to come into contact with a hydrate semi-large-cage. The distance between the amide of PVCaps and hydrate is about 4 Å and exceeds the range of a general hydrogen bond (3.5 Å), which proves that the non-binding-hydrate sites of PVCaps exist. On the other hand, the amide of PVCaps is at the intersection of the solid-liquid interface but has no adsorption affinity for hydrate, so this adsorption pattern indicates that the PVCaps at the hydrate interface are not stable. Due to this unstable adsorption, a repeated hydrate destruction phenomenon was revealed by the identification algorithm of hydrate and the calculation of the local number density of methane. The statistical evolution of water rings further proved the existence of non-binding-hydrate sites in PVCaps and the inhibition mechanism to destroy the hydrate cages by PVCaps. This unstable adsorption mechanism may shed light on the development of novel efficient KHIs.


A bead-based method for multiplexed identification and quantitation of DNA sequences using flow cytometry.
A new multiplexed, bead-based method which utilizes nucleic acid hybridizations on the surface of microscopic polystyrene spheres to identify specific sequences in heterogeneous mixtures of DNA sequences is described. The method consists of three elements: beads (5.6-microm diameter) with oligomer capture probes attached to the surface, three fluorophores for multiplexed detection, and flow cytometry instrumentation. Two fluorophores are impregnated within each bead in varying amounts to create different bead types, each associated with a unique probe. The third fluorophore is a reporter. Following capture of fluorescent cDNA sequences from environmental samples, the beads are analyzed by flow cytometric techniques which yield a signal intensity for each capture probe proportional to the amount of target sequences in the analyte. In this study, a direct hybrid capture assay was developed and evaluated with regard to sequence discrimination and quantitation of abundances. The target sequences (628 to 728 bp in length) were obtained from the 16S/23S intergenic spacer region of microorganisms collected from polluted groundwater at the nuclear waste site in Hanford, Wash. A fluorescence standard consisting of beads with a known number of fluorescent DNA molecules on the surface was developed, and the resolution, sensitivity, and lower detection limit for measuring abundances were determined. The results were compared with those of a DNA microarray using the same sequences. The bead method exhibited far superior sequence discrimination and possesses features which facilitate accurate quantitation.


Low-Z target optimization for spatial resolution improvement in megavoltage imaging.
Recently, several authors have shown contrast improvements in megavoltage portal imaging and cone-beam computed tomography using low atomic number (Z) targets. This work compliments previous studies by investigating the effects of varying different beam production parameters including target atomic number, target thickness, and incident electron energy on spatial resolution. Target materials of beryllium, aluminum, and tungsten were investigated over a range of thicknesses between 10% and 100% of the continuous slowing down approximation range of electrons. Incident electron kinetic energies of 4.5 and 7.0 MeV were used, in conjunction with custom targets installed above the carousel of a modern radiotherapy linear accelerator. Monte Carlo simulations of the accelerator were constructed and compared to the experimental results. The results showed that thinner targets, as well higher incident electron energies, generally produce more favorable modulation transfer function (MTF) curves. Due to an MTF dependence of the detector system on the photon energy, the experimental results showed that low-Z targets produced superior MTF curves. Simulations showed 14.5% and 21.5% increases in f50 for the 7.0 and 4.5 MeV targets (A1; 60% R% CSDA), respectively, when moved from the carousel to the location of the clinical target. f50 values for the custom targets were compared to the clinical 6 MV beam and were found to be between 10.4% lower (4.5 MeV/W) and 15.5% higher (7.0 MeV/Be). Integration of low-Z external targets into the treatment head of a medical linear was achieved with only minor modifications. It was shown that reasonably high resolution images on par or better than those acquired with the clinical 6 MV beam can be achieved using external low-Z targets.